Efficacy and Safety of 2 Raltegravir Doses in Naive HIV-1-infected Patients Receiving Rifampin for Active Tuberculosis

• Status: Completed
• Trial end date: 2012-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Raltegravir is a potent antiretroviral agent that could be used as an alternative to efavirenz in HIV-1 infected patients with tuberculosis. However due to pharmacokinetic interactions, the optimal dose of raltegravir to be used in combination with rifampin is currently unknown.

This phase II open-label randomized multicenter trial is designed to estimate the antiviral efficacy of two doses of raltegravir and one dose of efavirenz at week 24, in HIV-1 naive patients co-infected with active tuberculosis (TB) treated with rifampin.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases; French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Collaborators: Gilead Sciences; Merck Sharp & Dohme Corp.
• Treatments: Efavirenz; Lamivudine; Raltegravir Potassium; Rifampin; Tenofovir

Criteria

Inclusion Criteria:

• Adult patients (at least 18 years old)

• Plasma HIV RNA > 1000 copies/ml

• HIV-1-infection confirmed by ELISA and Western blot or Immunofluorescence

• ART naïve patients or

• ART for less than 3 months and more than 6 months ago ; an HIV resistance genotype at baseline showing no mutation to NNRTI and TDF or 3TC will be required

• For women of childbearing age, negative urinary test for pregnancy and to accept contraceptive methods: condom use and intra-uterine device when possible or declare no wish of pregnancy in the coming year.

• Confirmed or probable TB

• TB treatment including rifampin started since 2 to 8 weeks before randomisation

• Signed informed consent form

• For French patients, to be affiliated to the National Health Care System

Exclusion Criteria:

• HIV-2 infection (single or with HIV-1)

• Woman who is pregnant or likely to become so, is breastfeeding or refuses to use contraception

• ALT>2.5N, Hb <7g/dl, neutrophils < 750/mm3, platelet<50 000/mm3, bilirubin >5N, lipase >3N

• Creatinine clearance <60ml/min as assessed by the Cockcroft method

• Ongoing psychiatric pathology or any condition (including, but not limited to, the consumption of alcohol or drugs) which might, in the investigator's opinion, compromise the safety of treatment and/or patient compliance with the protocol

• Concomitant treatments including phenytoin or phenobarbital (compounds interacting with UGT1A1)

• Prior TB with a Mycobacterium tuberculosis strain resistant to rifampin

• TB treatment started for more than 8 weeks before randomisation